Implantation is very effective for treating deficiency occurred in part of tissues or irreversible function deficiency. For avoiding the problem of immune incompatibility known as rejection, in this case, it is preferable to transplant the tissue coming from other regions of the patient or his relatives, namely allotransplantation. However, such favorable implanting tissues are not always available. So, such studies for providing implantable artificial tissues have heretofore been made.
First approach for getting artificial tissues free of rejection is to provide the material having low histological reactivity, namely the material which fails to sensitize the tissue and immunocellular system. An example of this approach is the study to enhence hydrophobicity of the synthetic polymer material represented by polyurethanes.
Second approach is to provide the material which is capable of assimilating rapidly into the tissue before inducing the immunoreaction thereby functioning as a part of an organ. More particularly, it is to construct the tissue similar to connective tissues by penetrating such a cell having the tissue-healing function as fibroblast into the material coming from living bodies such as collagen. Since the new tissue thus formed is no longer not-self, no immune incompatibility would take place. Therefore, it can be said that this approach is more ideal than the first approach.
However, said second approach has the following defects.
Artificial materials consisting of collagen or the like derived from living bodies show high affinity to cellular tissues, but would be easily decomposed by collagenase or other enzymes within the living bodies. Therefore, there cannot be sufficiently kept the time for the penetration of fibroblast or the like to construct new tissues. So it is necessary to enforce the physical properties of the material by introducing cross-linking with any means, in order that the material may resist against the decomposition due to collagenase. Dehydrating cross-linking under heating or chemical cross-linking with chemicals can be adopted therefore. Of these cross-linking methods, the dehydrating cross-linking is safer than the chemical treatment, but less resistant against collagenase than the chemical cross-linking. Therefore, it is general that the chemical cross-linking is adopted singly, otherwise a combination of the chemical cross-linking and the dehydrating cross-linking is adopted.
Resistance against collagenase is markedly improved by introducing the cross-linking structure by said methods. For example, when the cross-linking structure is introduced into a collagen by merely dehydrating the collagen under heating at 110.degree. C. in vacuum for 24 hours, the cross-linked collagen is dissolved within one day by allowing to stand at 37.degree. C. in 3 unit/ml collagenase solution. On the contrary, the collagen obtained by introducing the cross-linking structure with an isocyanate type cross-linking agent does not show any change on appearance in 7 days even by allowing to stand still at 37.degree. C. in 1000 unit/ml collagenase solution.
On the other hand, introduction of said strong cross-linking structure would lower markedly the good affinity to cells or tissues, which is an inherent property of the collagen. Therefore, the penetration of cells would be inhibited to accompany a problem that the new desired tissues could not be formed.
As stated above, it is difficult to suffice both the requirement of good resistance to enzymes and the requirement of good affinity to cells or tissues in materials derived from living bodies such as collagen. Therefore, while the second approach is very attractive, no medical material sufficing the requirements has been developed yet.
The cell-penetrable medical material may be considered to be very useful as coating material for imbedding artificial organs or artificial vessels. However, its use as artificial skin is more realizable and effective.
Artificial skin is an artificial medical material used for coating temporarily or eternally the injured region in order to prevent bacterial infections or overflowing of the humor when any dermal tissue is injured by burning or ambustion. Thus, artificial skin is a replacement for autograft skin.
As a wound coating material which can be used for the same purpose as in artificial skin, gauze, absorbent cotton and the like are heretofor used. However, these materials have a disadvantage that they have low inhibitory ability against bacterial infections. In addition, because they absorb rapidly the exudate, the surface of wound would be dried so much and accompanied by pain, bleeding or the like in peeling them. Although sometimes an ointment or the like is used together for avoiding said problem, in this case there would take place another disadvantage that the exudate is so insufficiently absorbed that the surface of wound become excessively moist.
When the surface of a wound extends in a broad scope, the following coating films are used. First category includes silicone gauze, silicone rubber film, synthetic fiber sheet such as nylon, teflon or the like having velour-like superficial structure, and other synthetic materials. Second category includes lyophilizated pig's skin, chitin unwoven cloth, collagen film, polyamino acid sponge, mucopolysaccharide complex collagen film, and other materials derived from living bodies.
However, coating films made from said synthetic materials have disadvantages such as poor tight adhesion to the injured region and low steam permeability together with easy inclination to induce cracking. Further, said coating films derived from living bodies show comparatively better adaptability to living bodies but have difficulty in availability of raw material. Moreover, most of them have antigenicity as well as defects such as inclination to deteriorate by bacterial infection or contact with the exudate.
In addition to said coating films, certain complex film made from collagen-treated nylon mesh and silicone film has recently been developed and is commercially available. This complex film has favorable close adhesion to the surface of wound and appropriate water permeability. However, the complex film adheres to the surface of wound, because the granulation tissue enters into the nylon mesh in the course of curing. Since the nylon mesh remains in the granulation tissue without decomposition, after curing the complex film must be peeled together with remarkable pain.